The object of this project is to study the autonomic neuroendocrine control system for insulin and glucagon secretion and to determine the role of abnormalities in this system in the pathogenesis of diabetes mellitus, hypoglycemia and obesity. Studies are proposed in dogs, baboons and in man. In dogs, insulin and glucagon secretory rates will be assessed in vivo using an extra corporea flow system from the endocrine pancreas. The interaction between circulating glucose levels and the effects of selective parasympathetic and sympathetic nervous system activation will be measured. The importance of intact pancreatic nerves to endocrine pancreatic function will be evaluated after selective and total pancreatic denervation. The influence of insulin and glucagon concentration in the cerebrospinal fluid on reflex control of the endocrine pancreas will be determined. The effects of somatotropin release inhibiting factor (SRIF) on the secretion of pancreatic glucagon and insulin will be studied, and the locus and mechanism of action determined. In baboons it is proposed to examine the hypothesis that CSF hormone concentrations, particularly insulin, comprise a feedback system for the regulation of body weight. The effect of sight, smell and taste on pancreatic insulin and glucagon secretion will be measured in normal subjects and patients with diabetes, and obesity. Attempts will be made to bring pancreatic hormonal secretion under neutral stimulus control. The frequency of hyperglycemia in response to a standard environmental stress will be determined and the prognostic importance of stress induced hyperglycemia to the eventual development of overt diabetes mellitus assessed. BIBLIOGRAPHIC REFERENCES: Brunzell, J.D., Robertson, R.P., Lerner, R.L., Hazzard, W.R., Ensinck, J.W., Bierman, E.L. and Porte, D., Jr.: Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests. J. Clin. Endo. & Metab. 42:222-229, 1976. Robertson, R.P., Halter, J.B. and Porte, D., Jr.: A role for alpha adrenergic receptors in abnormal insulin secretion in diabetes mellitus. J. Clin. Invest. 57:791-795, 1976.